Pharmaceutical formulations can be designed as Multiple Unit Systems, an example of which is the so called MUPS (Multiple Unit Pellet Systems), where a dose is administrated for example as a tablet (tableted dosage form) or as a capsule (capsulated dosage form), each dose comprising a plurality of individual pellets or granules, referred to as subunits in the following. Each subunit carries one or more active drug or substance. A typical number of subunits in one dose form is 50, 100, 1000 or more.
Prior art discloses many different types of units intended for MUPS, such as for instance those described in U.S. Pat. No. 5,085,868. Usually, this type of formulation is preferred for controlled or sustained release formulations as well as for enteric coated formulations. The dose of the active substance may be administrated in the form of a tablet or a capsule or a like which disintegrates to make available a multitude of coated subunits, which release the active substance during the dissolution. Other prior-art MUPS are disclosed in U.S. Pat. No. 4,957,745, U.S. Pat. No. 4,927,640, U.S. Pat. No. 4,994,260, and U.S. Pat. No. 5,085,868.
Today, the common test procedure for determining the content, the functionality and/or the quality, etc. of MUPS is to analyze the formulation on a dose-level, i.e. to perform the analysis on a whole tablet or capsule. In conventional methods for determining the dose-level release profile the dosage form is placed in a test solution (in vitro testing) under controlled conditions, whereupon the test solution containing the dissolved active substance is analysed, typically by determining a release profile by the use of an optical absorption measurement.
However, MUPS are characterised in that the dose is the summation of the individual subunits and, therefore, by such prior-art test methods for analysing properties on dose-level of MUPS one only obtains a measurement of the cumulative release property of the entire subunit population. Variations in structure and release property between the individual subunits are not detectable, such as variations in film thickness, film defects, uneven subunit surfaces, deviations from spherical form of some subunits, etc. As a result, with presently available MUPS test methods it is not possible to identify the exact causes leading to unintended or intended variations on dose-level, such as variations in the release profile. Thus, even if it is possible to identify an "error" in the test results obtained by the conventional dose-level test methods, these methods will limit the possibilities to measure the product quality in terms of process parameters, i.e. the possibility to achieve detailed information is limited.
Dissolution testing provides essential information for the development of formulations, but the above limitations of the conventional test methods creates undesired limitations for obtaining a desired release profile. Especially, these limitations make it difficult to obtain a sufficiently exact and reproducible release profile.
Many mathematical models have been suggested in the literature for the description of release profiles. These models suffer from the drawback that it is difficult to correlate the obtained data, completely or partly, with a model when the result can be due to unknown sample variations.